The ultimate goal of this proposal is the development of antibody-directed enzyme-activated localization of radiopharmaceuticals to tumor cell- membranes by conversion of circulating hydrophilic radiolabeled prodrugs' to hydrophobic membrane-binding radiolabeled drugs at the tumor cell surface. This approach is meant to improve ont he delivery and specificity of radioisotope cancer diagnostic/therapies using tumor-specific monoclonal antibodies. We initially propose a prodrug that will be synthesized using solid-phase methodology. A metal-chelating agent will be attached to the free terminus of the resin-bound derivative to produce our drug while modification of hydroxyl functional groups will afford the prodrug. The enzyme will be conjugated to anti tumor mAb and tumor cell membrane-bound mAb/enzyme conjugates will be used to convert hydrophilic prodrugs to hydrophobic membrane-binding drugs in hive cell assays. Multiple turnovers of prodrug should localize larger doses of radiolabeled drug to tumor sites than previously possible by conventional radioimmunotherapy. Successful results of the proposed research may ultimately lead to clinical application as a diagnostic or therapy of cancer.